According to Steve Kenis, O'Toole's agent, the actor died Saturday at Wellington Hospital in London following a long unspecified illness.
O'Toole made a lasting impression in the 1962 film "Lawrence of Arabia", playing a mythical World War I soldier who leads an Arab rebellion against the Turks.
Playright Noel Coward said if O'Toole had been any prettier, they would have had to call the film "Florence of Arabia."
The actor earned an Oscar nomination for the role and became an international star.
During his lengthy career, O'Toole was nominated for an Academy Award seven more time for films including 1968's "Goodbye Mr. Chips" and "The Lion in Winter."
Off-screen, O'Toole was known for hard-drinking, carousing and being a ladies' man. He gave up drinking in the 1970s after suffering serious health problems.
The actor was last nominated for "Venus" in 2006. With that he set the record for most nominations without ever winning, though he accepted an honorary lifetime achievement Oscar.
O'Toole announced his retirement from acting in 2012, just weeks before his 80th birthday.
In 2011, O'Toole left his hand and footprints in cement in front of the TCL Chinese Theater in Hollywood.
His daughter, Kate, said in a statement the family was overwhelmed "by the outpouring of real love and affection being expressed towards him, and to us, during this unhappy time... In due course there will be a memorial filled with song and good cheer, as he would have wished."
The Associated Press contributed to this report